Daptomycin for the treatment of bacteraemia due to vancomycin-resistant enterococci

• VRE infection is an important clinical challenge due to the lack of reliable options against these organisms.
• DAP retains in vitro bactericidal activity against VRE, although this compound is not approved for infections caused by these organisms.
• The use of DAP was shortly followed by the development of DAP-resistance leading to therapeutic failures.
• DAP susceptible isolates with MICs close to the current breakpoint frequently harbour mutations associated with DAP-resistance.
• Alternatives for the treatment of DAP-resistant VRE are limited but the combination of DAP plus B-lactams is promising.

Treatment of severe infections caused by vancomycin-resistant enterococci (VRE) is challenging due to the scarcity of reliable therapeutic alternatives. In this context, daptomycin (DAP), a lipopeptide antibiotic, has emerged as an interesting alternative as it is one of the few compounds that retain in vitro bactericidal activity against VRE isolates, although it has not been approved for this purpose by regulatory agencies. In this review, we will summarise the clinical, animal and in vitro evidence evaluating the efficacy of DAP for the management of deep-seated VRE infections. In addition, we will address important clinical concerns such as the emergence of DAP resistance during therapy and reports of therapeutic failure with DAP monotherapy. Finally, we will discuss possible future strategies (such as the use of higher doses and/or combination therapies) to optimise the use of this antibiotic against VRE.